Development of a risk-predicting score for hip preservation with bone grafting therapy for osteonecrosis.

Identification and differentiation of appropriate indications on hip preserving with bone grafting therapy remains a crucial challenge in the treatment of osteonecrosis of the femoral head (ONFH). A prospective cohort study on bone grafting therapy for ONFH aimed to evaluate hip survival rates, and to establish a risk scoring derived from potential risk factors (multivariable model) for hip preservation. Eight variables were identified to be strongly correlated with a decreased rate of hip survival post-therapy, and a comprehensive risk scoring was developed for predicting hip-preservation outcomes. The C-index stood at 0.72, and the areas under the receiver operating characteristics for the risk score's 5- and 10-year hip failure event predictions were 0.74 and 0.72, respectively. This risk score outperforms conventional methods in forecasting hip preservation. Bone grafting shows sustained benefits in treating ONFH when applied under the right indications. Furthermore, the risk scoring proves valuable as a decision-making tool, facilitating risk stratification for ONFH treatments in future.

Modeling of large-scale hoxbb cluster deletions in zebrafish uncovers a role for segmentation pathways in atrioventricular boundary specification.

Hox genes orchestrate the segmental specification of the muscular circulatory system in invertebrates but it has not proven straightforward to decipher segmental parallels in the vertebrate heart. Recently, patients with HOXB gene cluster deletion were found to exhibit abnormalities including atrioventricular canal defects. Using CRISPR, we established a mutant with the orthologous hoxbb cluster deletion in zebrafish. The mutant exhibited heart failure and atrioventricular regurgitation at 5 days. Analyzing the four genes in the hoxbb cluster, isolated deletion of hoxb1b-/- recapitulated the cardiac abnormalities, supporting hoxb1b as the causal gene. Both in situ and in vitro data indicated that hoxb1b regulates gata5 to inhibit hand2 expression and ultimately is required to pattern the vertebrate atrioventricular boundary. Together, these data reveal a role for segmental specification in vertebrate cardiac development and highlight the utility of CRISPR techniques for efficiently exploring the function of large structural genomic lesions.

Energetic evaluation of phenol wastewater treatment by reverse electrodialysis reactor using different anodes.

Efficient electrode materials are essential to convert salinity gradient energy into oxidative degradation energy and electrical energy by reverse electrodialysis reactor (REDR). In this context, comparative experiments of REDR using different anodes (Ti/IrO2-RuO2, Ti/PbO2 and Ti/Ti4O7) were conducted. The effects of output current and electrode rinse solution (ERS) flowrate on mineralization efficiency and energy output were discussed. Results demonstrated that the COD removal rate(ηCOD) rose almost linearly with output current and ERS flowrate when using Ti/Ti4O7 anode, but excessive operating conditions caused a slow increase or even decrease of ηCOD when using Ti/IrO2-RuO2 or Ti/PbO2 anodes. The order of electrode system potential loss (Eele) for the three anodes was Ti/Ti4O7> Ti/PbO2> Ti/IrO2-RuO2. High Eele was beneficial to ηCOD but had a negative effect on the net output power (Pnet) of REDR. Regardless of the applied anodes, increasing the current and decreasing the ERS flowrate was detrimental to Pnet due to higher Eele. Based on these findings, four energy efficiency parameters were defined to evaluate energy recovery from multiple perspectives by linking energy output with mineralization capacity. They were electrode efficiency (ηele), energy efficiency (EE), general current efficiency (GCE) and energy consumption (EC), respectively. Results showed that REDR with Ti/Ti4O7 anodes and suitable operating conditions achieved the optimal energy indicators and mineralization efficiency, which provided an efficient and economical option for wastewater treatment and energy recovery.

Autologous Costal Cartilage Grafting for a Large Osteochondral Lesion of the Femoral Head: A 1-Year Single-Arm Study with 2 Additional Years of Follow-up.

BACKGROUND: There is currently no ideal treatment for osteochondral lesions of the femoral head (OLFH) in young patients. METHODS: We performed a 1-year single-arm study and 2 additional years of follow-up of patients with a large (defined as >3 cm 2 ) OLFH treated with insertion of autologous costal cartilage graft (ACCG) to restore femoral head congruity after lesion debridement. Twenty patients ≤40 years old who had substantial hip pain and/or dysfunction after nonoperative treatment were enrolled at a single center. The primary outcome was the change in Harris hip score (HHS) from baseline to 12 months postoperatively. Secondary outcomes included the EuroQol visual analogue scale (EQ VAS), hip joint space width, subchondral integrity on computed tomography scanning, repair tissue status evaluated with the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score, and evaluation of cartilage biochemistry by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) and T2 mapping. RESULTS: All 20 enrolled patients (31.02 ± 7.19 years old, 8 female and 12 male) completed the initial study and the 2 years of additional follow-up. The HHS improved from 61.89 ± 6.47 at baseline to 89.23 ± 2.62 at 12 months and 94.79 ± 2.72 at 36 months. The EQ VAS increased by 17.00 ± 8.77 at 12 months and by 21.70 ± 7.99 at 36 months (p < 0.001 for both). Complete integration of the ACCG with the bone was observed by 12 months in all 20 patients. The median MOCART score was 85 (interquartile range [IQR], 75 to 95) at 12 months and 75 (IQR, 65 to 85) at the last follow-up (range, 24 to 38 months). The ACCG demonstrated magnetic resonance properties very similar to hyaline cartilage; the median ratio between the relaxation times of the ACCG and recipient cartilage was 0.95 (IQR, 0.90 to 0.99) at 12 months and 0.97 (IQR, 0.92 to 1.00) at the last follow-up. CONCLUSIONS: ACCG is a feasible method for improving hip function and quality of life for at least 3 years in young patients who were unsatisfied with nonoperative treatment of an OLFH. Promising long-term outcomes may be possible because of the good integration between the recipient femoral head and the implanted ACCG. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Electrochemical removal of synthetic methyl orange dyeing wastewater by reverse electrodialysis reactor: Experiment and mineralizing model.

In this paper, the synthetic methyl orange (MO) dyeing wastewater treated by a reverse electrodialysis reactor (REDR) with 40 member pairs was investigated first. The boron-doped diamond (BDD) and carbon felt were adopted as an anode and a cathode in the REDR. The influences of operation parameters on the chemical oxygen demand (COD) removal efficiency were detected and explored. Then, a mathematical model of organic mineralizing was developed for the REDR to predict the variation of COD removal efficiency with treating time under the different operation conditions. Finally, the energy consumption of the wastewater treated by the REDR was analyzed. The results showed that raising the working fluid flowing velocity and electrode rinse solution flowrate improved the COD removal efficiency and instantaneous current efficiency (ICE), and reduced the total energy consumption (TEC) of the REDR. Raising the initial MO concentration could significantly reduce the TEC despite the COD removal efficiency being near. Since the main energy consumed by the REDR was salinity gradient energy (SGE) from waste heat conversion or the natural environment, the energy cost of REDR treating wastewater has been reduced significantly.

Internal fixation using fully threaded cannulated compression screws for fresh femoral neck fractures in adults.

OBJECTIVES: Internal fixation with multiple cannulated compression screws is an optional treatment for femoral neck fracture. Recently, fully threaded cannulated compression screws (FTCCS) have been introduced to fix fresh femoral neck fractures (FNF). The purpose of this study was to investigate the effectiveness of FTCCS. PATIENTS AND METHODS: Patients with FNF fixed by multiple FTCCS from February 1st, 2014 to August 31st, 2017 were included in this study. They were followed for at least 12 months postoperatively. Nonunion, osteonecrosis of the femoral head (ONFH), fixation failure, reoperation, and femoral neck shortening (FNS) were used to evaluate the outcomes. Risk factors including age, sex, fracture side, fracture displacement, fracture stability, fixation configuration, and screw numbers were analyzed. RESULTS: A total of 113 patients including 67 males and 46 females with an average age of 48.4 ± 13.4 years were included. The mean duration of follow-up was 27.1 months (range: 12-51 months). The incidence of nonunion, ONFH, fixation failure, and reoperation was 15.9%, 22.1%, 8.8%, and 24.8%, respectively. The rates of nonunion and reoperation were significantly higher in displaced fractures and unstable fractures. And patients with an unstable fracture had a higher risk of internal fixation failure. The median length of FNS was 2.9 mm (interquartile range: 0.9-6.5 mm, range: 0-17.5 mm). Age was a significant risk factor for FNS. CONCLUSIONS: The screw fixation method with FTCCS provided encouraging clinical results which may be a rational choice for the treatment of fresh FNF. Displaced fractures and unstable fractures were attributed to the higher incidence of complications. TRIAL REGISTRATION: ChiCTR, ChiCTR1800017200. Registered 17 July 2018-Retrospectively registered, http: www.chictr.org.cn/showprojen.aspx?proj=29182 .

Precise Dose of Folic Acid Supplementation Is Essential for Embryonic Heart Development in Zebrafish.

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. Moreover, we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days post fertilization (dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5 dpf. The expression levels of cardiac marker genes hand2, gata4, and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. Furthermore, our results reveal that folic acid has a dose-dependent effect on early cardiac development. Precise dosage of folic acid supplementation is crucial for the embryonic development of organisms.

Revision surgery due to failed internal fixation of intertrochanteric femoral fracture: current state-of-the-art.

Failed treatment of intertrochanteric (IT) femoral fractures leads to remarkable disability and pain, and revision surgery is frequently accompanied by higher complication and reoperation rates than primary internal fixation or primary hip arthroplasty. There is an urgent need to establish a profound strategy for the effective surgical management of these fragile patients. Salvage options are determined according to patient physiological age, functional level, life expectancy, nonunion anatomical site, fracture pattern, remaining bone quality, bone stock, and hip joint competency. In physiologically young patients, care should be taken to preserve the vitality of the femoral head with salvage internal fixation; however, for the elderly population, conversion arthroplasty can result in early weight bearing and ambulation and eliminates the risks of delayed fracture healing. Technical challenges include a difficult surgical exposure, removal of broken implants, deformity correction, critical bone defects, poor bone quality, high perioperative fracture risk, and prolonged immobilization. Overall, the salvage of failed internal fixations of IT fractures with properly selected implants and profound techniques can lead to the formulation of valuable surgical strategies and provide patients with satisfactory clinical outcomes.

Bone marrow lesion on magnetic resonance imaging indicates the last chance for hip osteonecrosis treated with vascularized fibular grafting before collapse.

PURPOSE: Timing of surgery is the most critical prognostic factor for hip osteonecrosis treated with free vascularized fibular grafting (FVFG). Bone marrow lesion (BML) on MRI usually occurs immediately before femoral head collapse. We conducted a retrospective cohort study to evaluate whether the noncollapsed hips with BML can benefit from FVFG. METHODS: Consecutive patients undergoing modified FVFG were identified from our clinical repository between January 2014 and December 2014. Based on whether BML was pre-operatively detected, the four year radiographic and clinical outcomes were compared. RESULTS: In the BML cohort, 22 of 53 hips (42%) showed radiographic signs of osteonecrosis progression, which was significantly higher than that in the control cohort (8 of 49, 16%; P = 0.005). The BML hips showed a significantly lower pre-operative Harris Hip Score (HHS) than those without BML (77.8 vs. 85.5, P = 0.046), whereas no such difference was observed in the final HHS or its post-operative improvement (HHS 90 vs. 94, P = 0.397; HHS improvement 12 vs. 8, P = 0.067). In the subgroup of patients with a pre-operative HHS lower than 80, BML hips were associated with a slightly lower final HHS than hips without BML. Four of 5 (80%) failed hips with BML had a poor pre-operative hip function. CONCLUSION: BML indicates the last chance for a reproducible improvement in the treatment of hip osteonecrosis with FVFG before collapse. However, the concomitant lower pre-operative HHS (< 80) is a poor prognostic factor for BML-positive hips.

Autologous costal chondral transplantation and costa-derived chondrocyte implantation: emerging surgical techniques.

It is a great challenge to cure symptomatic lesions and considerable defects of hyaline cartilage due to its complex structure and poor self-repair capacity. If left untreated, unmatured degeneration will cause significant complications. Surgical intervention to repair cartilage may prevent progressive joint degeneration. A series of surgical techniques, including biological augmentation, microfracture and bone marrow stimulation, autologous chondrocyte implantation (ACI), and allogenic and autogenic chondral/osteochondral transplantation, have been used for various indications. However, the limited repairing capacity and the potential pitfalls of these techniques cannot be ignored. Increasing evidence has shown promising outcomes from ACI and cartilage transplantation. Nevertheless, the morbidity of autologous donor sites and limited resource of allogeneic bone have considerably restricted the wide application of these surgical techniques. Costal cartilage, which preserves permanent chondrocytes and the natural osteochondral junction, is an ideal candidate for the restoration of cartilage defects. Several in vitro and in vivo studies have shown good performance of costal cartilage transplantation. Although costal cartilage is a classic donor in plastic and cosmetic surgery, it is rarely used in skeletal cartilage restoration. In this review, we introduce the fundamental properties of costal cartilage and summarize costa-derived chondrocyte implantation and costal chondral/osteochondral transplantation. We will also discuss the pitfalls and pearls of costal cartilage transplantation. Costal chondral/osteochondral transplantation and costa-based chondrocytotherapy might be up-and-coming surgical techniques for recalcitrant cartilage lesions.

[Mid-term effectiveness of surgical hip dislocation for femoroacetabular impingement].

OBJECTIVE: To assess the mid-term effecitveness of femoroacetabular impingement (FAI) treated by surgical hip dislocation. METHODS: Between April 2014 and August 2015, 15 patients (16 hips) with FAI were enrolled in the study and treated with surgical hip dislocation. There were 12 males and 3 females with an average age of 36.6 years (range, 22-59 years). Among them, 14 cases involved in unilateral hip and 1 in bilateral hips. The mean disease duration was 28 months (range, 4-120 months). Preoperative visual analogue scale (VAS) score and Harris hip score were 7.9±1.0 and 44.1±9.3, respectively. RESULTS: All incisions healed by first intention. There was no main complication, such as vessel and nerve injuries and infection. All 15 patients were followed up 30-46 months (mean, 39.5 months). The VAS score was 2.5±1.6 at 3 months and 0.5±0.7 at last follow-up. The Harris score was 85.5±4.4 at 3 months and 95.6±3.9 at last follow-up. There were significant differences in two scores between pre- and post-operation and between 3 months and last follow-up ( P<0.05). The satisfaction rate of hip function was 93.8% (15/16) at last follow-up. X-ray examination showed that there was no sign of impingment at the femoral head and neck and acetabulum forming site of the affected hip joint, and no complication such as loosening of internal fixator, nonunion of osteotomy, avascular necrosis of femoral head, and heterotopic ossification occurred during follow-up. CONCLUSION: The surgical hip dislocation is a safe and effective way to treat FAI in the mid-term follow-up, which can repair torn labrum and trim acetabulum and femoral neck.

[Mid-term effectiveness of arthroscopic surgery for femoroacetabular impingement].

Objective: To assess the mid-term effectiveness of arthroscopic surgery in treatment of femoroacetabular impingement (FAI). Methods: Between July 2014 and December 2015, 131 patients (132 hips) with FAI were enrolled in this study. There were 68 males and 63 females with an average age of 42.5 years (range, 17-68 years). The FAI was located at left hip in 72 cases, right hip in 58 cases, and bilateral hips in 1 case. The mean disease duration was 35 months (range, 3-120 months). Under arthroscopy, the femoral neck osteoplasty and/or acetabular rim trimming were performed, then the torn labrum was repaired. At the same time, the iliopsoas tendon was divided and the torn round ligament was debrided. The effectiveness was assessed by the visual analogue scale (VAS) and the Harris hip score (HHS). Results: After operation, the perineum nerve palsy and numbness of dorsal feet occurred in 2 cases and 3 cases, respectively. There was no other complication. All patients were followed up 20-36 months (mean, 27.7 months). There were significant differences in the VAS scores and HHS scores between pre-operation, post-operative 3 months, and the last follow-up ( P<0.05). Imaging examination showed that joint interspace of the involved hip was normal, and there was no sign of impingement and osteoarthritis in the femoral neck or acetabulum. Conclusion: Arthroscopic labral repair and osteoplasty is an effective and safe management for FAI in the mid-term follow-up.

Reverse Less Invasive Stabilization System (LISS) Plating for Proximal Femur Fractures in Poliomyelitis Survivors: A Report of Two Cases.

BACKGROUND Poliomyelitis is a neuromuscular disease which causes muscle atrophy, skeletal deformities, and disabilities. Treatment of hip fractures on polio-affect limbs is unique and difficult, since routine fixation methods like nailing may not be suitable due to abnormal skeletal structures. CASE REPORT We report one femoral neck fracture and one subtrochanteric fracture in polio survivors successfully treated with reverse less invasive stabilization system (LISS) plating technique. Both fractures were on polio-affected limbs with significant skeletal deformities and low bone density. A contralateral femoral LISS plate was applied upside down to the proximal femur as an internal fixator after indirect or direct reduction. Both patients had uneventful bone union and good functional recovery. CONCLUSIONS Reverse LISS plating is a safe and effective technique to treat hip fractures with skeletal deformities caused by poliomyelitis.

Optimization of pure platelet-rich plasma preparation: A comparative study of pure platelet-rich plasma obtained using different centrifugal conditions in a single-donor model.

While it has been proved that centrifugal conditions for pure platelet-rich plasma (P-PRP) preparation influence the cellular composition of P-PRP obtained, the optimal centrifugal conditions to prepare P-PRP have not yet been identified. In the present study, platelet-containing plasma (PCP) was prepared with the first-spin of different double-spin methods and P-PRP was prepared with different double-spin methods. Whole-blood analysis was performed to evaluate the cellular composition of PCP and P-PRP. The basal and ADP-induced CD62P expression rates of platelets were assessed by flow cytometry to evaluate the function of platelets in PCP and P-PRP. Enzyme-linked immune sorbent assay was performed to quantify interleukin-1ß, tumor necrosis factor-α, platelet-derived growth factor AB and transforming growth factor ß1 concentrations of PCP and P-PRP. Correlations between the cellular characteristics and cytokine concentrations of P-PRP were analyzed by Pearson correlation analysis. Effects of P-PRP on the proliferation, survival and migration of human bone marrow-derived mesenchymal stem cells and human articular chondrocytes were evaluated by a Cell Counting Kit-8 assay, live/dead staining and Transwell assay, respectively. The results showed that centrifugation at 160 × g for 10 min and 250 × g for 15 min successively captured and concentrated platelets and growth factors significantly more efficiently with preservation of platelet function compared with other conditions (P<0.05). The correlation analysis showed that the similar leukocyte concentrations and leukocyte-reducing efficiencies resulted in similar pro-inflammatory cytokine concentrations in P-PRP (P>0.05) and the maximization of platelet concentration, platelet enrichment factor, platelet capture efficiency and platelet function resulted in the maximization of growth factor concentrations in P-PRP obtained using the optimal conditions (P<0.05). Compared with P-PRP obtained under other conditions, P-PRP obtained under the optimal conditions significantly promoted the proliferation and migration of cells (P<0.05) and did not alter cell survival (P>0.05). Therefore, centrifugation at 160 × g for 10 min and 250 × g for 15 min successively with removal of the buffy coat as a crucial step may provide an optimal preparation system of P-PRP for clinical application.

Combination of modified free vascularized fibular grafting and reverse Less Invasive Stabilization System (LISS) for the management of femoral neck nonunion in patients thirty years of age or younger.

Femoral neck nonunion (FNN) is a potential complication in patients with displaced femoral neck fractures, occurring in 33%. This may lead to early hip dysfunction or arthroplasty. Combination of modified free vascularized fibular grafting (FVFG) and a reverse LISS may provide a reasonable means to salvage a painless, functional and native hip. Between August 2010 and August 2012, sixteen patients with femoral neck nonunion were treated with a combined procedure involving modified free vascularized fibular grafting and a reverse LISS. The average age of them is 20.3 years (range 12.0-28.0 years). After removing old implants, the nonunion site was debrided, reduced and fixed with a LISS. The fibular grafts were compacted into a trough in the femoral neck. The Harris Hip score system was used to assess hip function and anteroposterior and frog-lateral hip roentgenograms were used to evaluate bone healing. All femoral neck nonunion healed without severe complications. The mean follow-up time was 32.9 months (range 23.0-47.0 months) and the average union time was 7.6 months (range 5.0-10.0 months). All coxa vara deformities and retroversions of the femoral head were corrected. The Harris hip scores (HHS) were improved 36.6 points on average (59.6 points preoperatively to 96.2 points postoperatively). No incidences of osteonecrosis of the femoral head were observed. The combined modified FVFG and reverse LISS plating is a suitable procedure for the management of femoral neck nonunion in patients younger than 30 years, especially for those patients with a revision history.

Prevalence of clinical anxiety, clinical depression and associated risk factors in chinese young and middle-aged patients with osteonecrosis of the femoral head.

OBJECTIVE: To investigate the prevalence of clinical anxiety and clinical depression in Chinese young and mid-aged patients with osteonecrosis of the femoral head (ONFH) and to analyze their potential risk factors. METHODS: Two hundred and sixteen Chinese patients with ONFH were consecutively enrolled in this cross-sectional study from January 2010 to December 2010. The Zung self-rating anxiety scale (SAS) and the Zung self-rating depression scale (SDS) were used to assess the prevalence of clinical anxiety and clinical depression. An additional questionnaire containing seventeen items of potential risk factors was completed by all patients. Binary logistic regression analysis was employed to reveal potential risk factors of anxiety and depression. RESULTS: The prevalence of clinical anxiety and clinical depression was 20.4% and 21.8% in Chinese young and middle-aged patients with ONFH, respectively. Binary regression analysis showed that independent risk factors correlated with high incidence of clinical anxiety included involved femoral head (OR = 3.168, 95% CI: 1.496 - 6.708) and stages of ONFH (ORIV-V / II = 5.383, 95% CI: 1.664-17.416). Independent risk factors correlated with high incidence of depression included gender (OR = 2.853, 95% CI: 1.467-5.778), comorbid diseases (OR = 4.243, 95% CI: 1.940-9.278) and stages of the disease (OR IV-V/II = 16.963, 95% CI: 4.404-65.331). CONCLUSIONS: Patients with bilateral ONFH are inclined to have clinical anxiety, while female patients and patients with comorbid diseases might tend to get clinical depression. Advanced stages of ONFH are independent risk factors for both clinical anxiety and clinical depression.

Reference intervals of several renal and hepatic function parameters for apparently healthy adults from Eastern China.

BACKGROUND: Biochemical substances relating to renal and hepatic function are influenced not only by individual factors such as gender, lifestyle, and age but also by ecological factors, such as altitude, climate, and ethnic background. The purpose of the present study was to establish reference intervals for 16 biochemical substances relating to renal and hepatic function in healthy Chinese adults. METHODS: A total of 2,405 apparently healthy individuals (18-77 years of age) were chosen as reference individuals in the present study. The 16 biochemical substances relating to renal and hepatic function were analyzed using a HITACHI RL7600 analyzer. The reference intervals were established using nonparametric methods to estimate the 2.5 and 97.5 percentiles of the distribution as the lower and the upper limits, respectively. RESULTS: Age- and gender-appropriate reference intervals were established for some biochemical substances relating to renal and hepatic function in healthy Chinese adults. CONCLUSION: The reference intervals established in this study can provide a useful clinical tool for the assessment of the kidney and liver damage. In addition, the established reference intervals can be adopted in other clinical laboratories after further validation.

Lithium stimulates human bone marrow derived mesenchymal stem cell proliferation through GSK-3ß-dependent ß-catenin/Wnt pathway activation.

Mesenchymal stem cells (MSCs) are multipotent cells that have been widely used in cell based transplantation therapy. The use of MSCs requires in vitro expansion in order to fulfill their regenerative capacity. Therefore the proliferative ability of MSCs is one of the key factors which determine MSC therapeutic efficacy. In the present study, we showed for the first time that lithium, a well-known antidepressant, reversibly promoted the proliferation of human bone marrow derived MSCs in vitro. MSCs treated with 5 mm lithium proliferated more rapidly than untreated cells without undergoing apoptosis. Lithium increased the proportion of cells in S phase as well as cyclin D1 expression. Mechanistic studies revealed that these effects were dependent upon the activation of the glycogen synthase kinase 3ß (GSK-3ß) mediated canonical Wnt pathway. Lithium induced Ser9 phosphorylation, which results in the inhibition of GSK-3ß activity, ß-catenin accumulation and Wnt pathway activation. Utilizing a specific GSK-3ß inhibitor SB216763 or siRNA-mediated inhibition of GSK-3ß produced effects similar to those induced by lithium. In contrast, either quercetin, an inhibitor of the ß-catenin/TCF pathway, or siRNA-mediated knockdown of ß-catenin abolished the proliferative effect of lithium, suggesting that lithium stimulates MSC proliferation via the GSK-3ß-dependent ß-catenin/Wnt pathway. Collectively, these studies elucidate a novel role of lithium, which may not only provide a simple and effective way to strengthen MSC transplantation therapy efficacy but also shed light on lithium's clinical application for the treatment of certain disorders resulting from ß-catenin/Wnt pathway suppression.

Modified surgical techniques of free vascularized fibular grafting for treatment of the osteonecrosis of femoral head: results from a series of 407 cases.

The goal for treatment of osteonecrosis of the femoral head (ONFH) is to relieve pain, preserve the contour of the femoral head, and delay the need for total hip arthroplasty. The free vascularized fibular grafting (FVFG) has been shown to support the subchondral architecture as well as restore local circulation for the necrotic femoral head in treatment of ONFH. This report aimed to present the clinical results of the use of a modified surgical technique of FVFG for treatment of ONFH. Four hundred and seven patients with 578 hips of ONFH were included. The patients' average age was 36.7 years old (ranging 19-55 years old). The disease was staged from II to V based on the Steinberg classification system. By the modified procedure, the vascularized fibular graft was harvested via a lateral incision with fibular osteotomy prior to the exposure of the vascular pedicle, and the removal of necrotic tissue and inset of graft were performed through an anterior approach. The operative time averaged 90 min for unilateral ONFH (ranging 75-110 min) and 190 min for simultaneous treatment of bilateral ONFH (ranging 160-230 min). The average length of follow-up was 5.0 years (ranging 3-10 years). The complications included one infection in one case, temporary loss of sensation of the thigh in eleven cases, and restricted motion of the great toe in nine cases. The Harris hip score of patients improved from 65.0 to 86.9 on average. Radiographic evaluation showed no changes in 331 hips (57.3%), improvement in 195 hips (33.7%) and necrosis progression in 52 hips (9.0%). Twenty-three hips (4.0%) in 20 patients had total hip arthroplasty during the period. These results show that the modified technique of the use of FVFG for treatment of ONFH yields similar postoperative results in comparison to the traditional method.